title: Interactions between serotypes of dengue highlight epidemiological impact of cross-immunity.
abstract: Dengue, a mosquito-borne virus of humans, infects over 50 million people annually. Infection with any of the four dengue serotypes induces protective immunity to that serotype, but does not confer long-term protection against infection by other serotypes. The immunological interactions between serotypes are of central importance in understanding epidemiological dynamics and anticipating the impact of dengue vaccines. We analysed a 38-year time series with 12 197 serotyped dengue infections from a hospital in Bangkok, Thailand. Using novel mechanistic models to represent different hypothesized immune interactions between serotypes, we found strong evidence that infection with dengue provides substantial short-term cross-protection against other serotypes (approx. 1-3 years). This is the first quantitative evidence that short-term cross-protection exists since human experimental infection studies performed in the 1950s. These findings will impact strategies for designing dengue vaccine studies, future multi-strain modelling efforts, and our understanding of evolutionary pressures in multi-strain disease systems.
authors.affiliation: Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA 01002, USA. nick@schoolph.umass.edu
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Reich
authors.forename: Sourya
authors.initials: S
authors.lastname: Shrestha
authors.forename: Aaron A
authors.initials: AA
authors.lastname: King
authors.forename: Pejman
authors.initials: P
authors.lastname: Rohani
authors.forename: Justin
authors.initials: J
authors.lastname: Lessler
authors.forename: Siripen
authors.initials: S
authors.lastname: Kalayanarooj
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Yoon
authors.forename: Robert V
authors.initials: RV
authors.lastname: Gibbons
authors.forename: Donald S
authors.initials: DS
authors.lastname: Burke
authors.forename: Derek A T
authors.initials: DA
authors.lastname: Cummings
mesh_terms: D000818:Animals; D056738:Cross Protection; D003429:Cross Reactions / Q000276:immunology; D009033:Culicidae / Q000821:virology; D003715:Dengue / Q000453:epidemiology / Q000235:genetics / Q000821:virology; D003716:Dengue Virus / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D018448:Models, Immunological; D012189:Retrospective Studies; D013785:Thailand / Q000453:epidemiology
keywords: cross-protection; dengue; infectious disease modelling; time-series models